Quinine is a common cause of drug-induced thrombocytopenia and the most common cause of druginduced thrombotic microangiopathy. Other quinine-induced systemic disorders have been described. To understand the complete clinical spectrum of adverse reactions to quinine we searched 11 databases for articles that provided sufficient data to allow evaluation of levels of evidence supporting a causal association with quinine. Three reviewers independently determined the levels of evidence, including both immune-mediated and toxic adverse reactions. The principal focus of this review was on acute, immunemediated reactions. The source of quinine exposure, the involved organ systems, the severity of the adverse reactions, and patient outcomes were documented. One hundred-fourteen articles described 142 patients with definite or probable evidence for a causal association of quinine with acute, immune-mediated reactions. These reactions included chills, fever, hypotension, painful acral cyanosis, disseminated intravascular coagulation, hemolytic anemia, thrombocytopenia, neutropenia, acute kidney injury, rhabdomyolysis, liver toxicity, cardiac ischemia, respiratory failure, hypoglycemia, blindness, and toxic epidermal necrolysis. One hundred-two (72%) reactions were caused by quinine pills; 28 (20%) by quinine-containing beverages; 12 (8%) by five other types of exposures. Excluding 41 patients who had only dermatologic reactions, 92 (91%) of 101 patients had required hospitalization for severe illness; 30 required renal replacement therapy; three died. Quinine, even with only minute exposure from common beverages, can cause severe adverse reactions involving multiple organ systems. In patients with acute, multi-system disorders of unknown origin, an adverse reaction to quinine should be considered.

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Objectives: Oxytocin (OT) has a well-established role in reproductive behaviours; however, it recently emerged as an important regulator of energy homeostasis. In addition to central nervous system (CNS), OT is found in the plasma and OT receptors (OT-R) are found in peripheral tissues relevant to energy balance regulation.Here, we aim to determine whether peripheral OT-R activation is sufficient to alter energy intake and expenditure. Methods and Results:We first show that systemic OT potently reduced food intake and food-motivated behaviour for a high-fat reward in male and female rats. As it is plausible that peripherally, intraperitoneally (IP) injected OT crosses the blood-brain barrier (BBB) to produce some of the metabolic effects within the CNS, we screened, with a novel fluorescently labelled-OT (fAF546-OT, Roxy), for the presence of IPinjected Roxy in CNS tissue relevant to feeding control and compared such with BBB-impermeable fluorescent OT-B 12 (fCy5-OT-B 12; BRoxy). While Roxy did penetrate the CNS, BRoxy did not. To evaluate the behavioural and thermoregulatory impact of exclusive activation of peripheral OT-R, we generated a novel BBBimpermeable OT (OT-B 12 ), with equipotent binding at OT-R in vitro. In vivo, IPinjected OT and OT-B 12 were equipotent at food intake suppression in rats of both sexes, suggesting that peripheral OT acts on peripheral OT-R to reduce feeding behaviour. Importantly, OT induced a potent conditioned taste avoidance, indistinguishable from that induced by LiCl, when applied peripherally. Remarkably, and in contrast to OT, OT-B 12 did not induce any conditioned taste avoidance. Limiting the CNS entry of OT also resulted in a dose-dependent reduction of emesis in male shrews. While both OT and OT-B 12 proved to have similar effects on body temperature, only OT resulted in home-cage locomotor depression.

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ImportanceMost patients presenting to US emergency departments (EDs) with acute pulmonary embolism (PE) are hospitalized, despite evidence from multiple society-based guidelines recommending consideration of outpatient treatment for those with low risk stratification scores. One barrier to outpatient treatment may be clinician concern regarding findings on PE-protocol computed tomography (CTPE), which are perceived as high risk but not incorporated into commonly used risk stratification tools.ObjectiveTo evaluate the association of concerning CTPE findings with outcomes and treatment of patients in the ED with acute, low-risk PE.Design, Setting, and ParticipantsThis cohort study used a registry of all acute PEs diagnosed in the adult ED of an academic medical center from October 10, 2016, to December 31, 2019. Acute PE cases were divided into high- and low-risk groups based on PE Severity Index (PESI) class alone or using a combination of PESI class and biomarker results. The low-risk group was further divided based on the presence of concerning CTPE findings: (1) bilateral central embolus, (2) right ventricle–to–left ventricle ratio greater than 1.0, (3) right ventricle enlargement, (4) septal abnormality, or (5) pulmonary infarction. Data analysis was conducted from June to October 2022.Main Outcomes and measuresThe primary outcome was all-cause mortality at 7 and 30 days. Secondary outcomes included hospitalization, length of stay, need for intensive care, use of echocardiography and/or bedside ultrasonography, and activation of the PE response team (PERT) .ResultsOf 817 patients (median [IQR] age, 58 [47-71] years; 417 (51.0%) female patients; 129 [15.8%] Black and 645 [78.9%] White patients) with acute PEs, 331 (40.5%) were low risk and 486 (59.5%) were high risk by PESI score. Clinical outcomes were similar for all low-risk patients, with no 30-day deaths in the low-risk group with concerning CTPE findings (0 of 151 patients) vs 4 of 180 (2.2%) in the low-risk group without concerning CTPE findings and 88 (18.1%) in the high-risk group (P < .001). Low-risk patients with concerning CTPE findings were less frequently discharged from the ED than those without concerning CTPE findings (3 [2.0%] vs 14 [7.8%]; P = .01) and had more frequent echocardiography (87 [57.6%] vs 49 [27.2%]; P < .001) and PERT activation for consideration of advanced therapies (34 [22.5%] vs 11 [6.1%]; P < .001).Conclusions and RelevanceIn this single-center study, CTPE findings widely believed to confer high risk were associated with increased hospitalization and resource utilization in patients with low-risk PE but not short-term adverse clinical outcomes.

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Iliocaval thrombosis is a major source of morbidity for patients, with a range of clinical presentations, including recurrent lower extremity deep venous thrombosis and postthrombotic syndrome. Endovascular reconstruction of chronic iliocaval occlusion has been demonstrated to be a technically feasible procedure that provides long-lasting symptom relief in combination with antithrombotic therapy and close clinical monitoring. Herein, we describe the etiologies of iliocaval thrombosis, patient assessment, patient management prior to and after intervention, procedural techniques, and patient outcomes.

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